Bio-electric field enhancement: the influence on hyaluronan mediated motility receptors in human breast carcinoma.

Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred. Therefore, RHAMM has been shown to contribute to both natural healing mechanisms and cancer cell pathology. RHAMM is expressed in breast tissue and forms a polarity normalizing complex with BRCA1. Mutations of BRCA1 have been associated with a loss of apicobasal cell polarity along with a subsequent increased expression of RHAMM. Here we show how a human breast carcinoma cell line was maintained in media prepared with a dilute saline solution that had been exposed to a dielectrophoretic (DEP) electromagnetic field (EMF) generated by 3 amperes of direct current (dc) to a device housing an array of conductive rings. This Bio-electric Field Enhancement (BEFE) device has been available commercially for use in baths/footbaths since 1996 and consumers claim that it provides health benefits ranging from lowering blood pressure to faster wound healing. Our studies showed a significant inhibition of growth of human breast carcinoma MDA-MB-231 cells when they were maintained in media prepared with dc-DEP EMF force treated dilute saline while no growth inhibition occurred when the same cells were maintained in identically prepared but untreated media. Importantly, no growth inhibition was observed in human epithelial MCF-10A cells when grown in either treated or untreated media. Also, mitotic spindle formation was inhibited in the human breast carcinoma when they were grown in dc-DEP EMF force treated media. To determine if any gene expression changes contributed to the selective growth inhibition and absent mitotic spindle formation in the human breast carcinoma grown in the treated media, we employed microarray analysis and found that there was large-scale transcriptional reprogramming of the tumor cells grown in the treated media with over 1,000 genes up- or down-regulated over 2-fold, whereas the non-cancerous MCF-10A cells showed relatively modest changes in gene expression. Of the genes affected in the MDA-MB-231 cells, the significance of down-regulation of HMMR is discussed. The ability to enhance cell polarity through the application of this dc-DEP EMF force may offer another way to stabilize HMMR and differentially modulate its expression in cancerous and noncancerous cells.